2021
DOI: 10.3389/fphar.2021.731798
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PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy

Abstract: Programmed death protein 1 (PD1) is a common immunosuppressive member on the surface of T cells and plays an imperative part in downregulating the immune system and advancing self-tolerance. Its ligand programmed cell death ligand 1 (PDL1) is overexpressed on the surface of malignant tumor cells, where it binds to PD1, inhibits the proliferation of PD1-positive cells, and participates in the immune evasion of tumors leading to treatment failure. The PD1/PDL1-based pathway is of great value in immunotherapy of … Show more

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Cited by 207 publications
(198 citation statements)
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References 102 publications
(102 reference statements)
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“…Furthermore, the overexpression of PD-L1 is correlated with poor prognosis in many cancers (291)(292)(293)(294). In order to block the interaction between PD-1 and PD-L1, various mAbs, such as nivolumab, pembrolizumab, avelumab, lambrolizumab, and atezolizumab, have been developed (295). After encouraging results from different clinical trials, the FDA granted accelerated approval to nivolumab for the treatment of advanced melanoma in 2014 (296), and advanced squamous NSCLC in 2015 (297).…”
Section: Overcoming Inhibition By Negative Immune Checkpointsmentioning
confidence: 99%
“…Furthermore, the overexpression of PD-L1 is correlated with poor prognosis in many cancers (291)(292)(293)(294). In order to block the interaction between PD-1 and PD-L1, various mAbs, such as nivolumab, pembrolizumab, avelumab, lambrolizumab, and atezolizumab, have been developed (295). After encouraging results from different clinical trials, the FDA granted accelerated approval to nivolumab for the treatment of advanced melanoma in 2014 (296), and advanced squamous NSCLC in 2015 (297).…”
Section: Overcoming Inhibition By Negative Immune Checkpointsmentioning
confidence: 99%
“…This interaction inhibits CD4+/CD8+ tumor-infiltrating T-lymphocytes (CD4+/CD8+ TILs), which results in a decrease in cytokines, such as Interleucin-2 (IL-2), interferon gamma (IFN-γ) and tumor necrosis factor (TNF). PD-L1 on the surface of tumor cells can be enhanced by IFN-γ produced by activated T-cells [ 10 ]. PD-L1 expression is upregulated through signaling pathways, including PI3K/Akt/mTOR and PD-L1-mediated immunoresistance could be suppressed by PI3K kinase pathway inhibitors.…”
Section: Immune Checkpoint Expression In Connection With Clinical Features and The Therapeutic Efficacy Of Their Inhibitionmentioning
confidence: 99%
“…Monoclonal antibodies (mAbs) targeting critical immune checkpoints, such as PD-1/PD-L1 and CTLA-4, have significantly ameliorated the treatment of advanced solid tumors, such as lung (NSCLC), skin and liver cancers. Immune checkpoint inhibitors targeting and blocking the interaction of certain cell surface proteins, such as PD-1 expressed on diverse immune cells or PD-L1 expressed on cancer cells, act as brakes on immune responses [ 40 , 41 ]. A handful of mAbs directed against PD-1 or PD-L1 have been approved for cancer treatment, including pembrolizumab, nivolumab, atezolizumab, camrelizumab and others.…”
Section: The Tim-3 Immune Checkpoint and Its Targeting With Antibodiesmentioning
confidence: 99%